Candidemia, Candidiasis, Invasive
Conditions
Brief summary
This is a multicenter, randomized, double-blind study of two treatment regimens for invasive candidiasis including candidemia. Subjects will receive intravenous echinocandin followed by oral ibrexafungerp (SCY-078) vs intravenous echinocandin followed by oral fluconazole.
Interventions
DRUGSCY-078
Oral ibrexafungerp (SCY-078) as step-down therapy.
DRUGFluconazole
Oral fluconazole (SCY-078) as step-down therapy.
DRUGEchinocandin
Intravenous echinocandin
Sponsors
Scynexis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Subject is a male or female adult ≥ 18 years of age on the day the study informed consent is signed. * Subject has a diagnosis of candidemia and/or invasive candidiasis, defined as evidence of Candida spp in either a bloodstream or tissue culture from a normally sterile site (excluding eye, cardiac tissue, bone tissue, central nervous system or prosthetic device) collected ≤ 4 days (within 96 hours) prior to initiation of IV echinocandin accompanied by any related clinical signs and/or symptoms (e.g., fever \[on one occasion \> 38°C\], hypotension, or local signs of inflammation). Key
Exclusion criteria
* Subject has any of the following forms of invasive candidiasis at Screening: * Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed), * Osteomyelitis, * Endocarditis or myocarditis, * Meningitis, endophthalmitis, or any central nervous system infection, * Chronic disseminated candidiasis, * Urinary tract candidiasis due to ascending Candida infection secondary to unresolved obstruction or non-removeable device in the urinary tract, * Patients with a sole diagnosis of mucocutaneous candidiasis, i.e., oropharyngeal, esophageal, or genital candidiasis; or Candida lower urinary tract infection or Candida isolated solely from respiratory tract specimens, * Patients with concurrent invasive fungal infection other than Candida spp., e.g., cryptococcosis, mold infection or endemic fungal infection, * Patients who failed a previous antifungal therapy for the same infection, * Subject has an inappropriately controlled fungal disease source (e.g., indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained) that is likely to be the source of the candidemia or invasive candidiasis. * Subject has abnormal liver test parameters: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels \> 10-fold the upper limit of normal (ULN). * Subject has severe hepatic impairment and a history of chronic cirrhosis (Child-Pugh score \> 9). * Subject has received more than 48 hours of non-echinocandin antifungal therapy for the treatment of invasive candidiasis (including candidemia) within 96 hours preceding initiation of IV echinocandin. o Exception: Receipt of antifungal therapy to which any Candida spp. isolated in qualifying culture is not susceptible. * Baseline QTcF ≥ 500 msec.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality | Day 30 | The number and percentage of subjects in each treatment group who are alive and deceased in the ITT population. |
| Global Response at End of Treatment (EU European Medicines Agency [EMA] Only) | Up to 6 weeks | The percentage of subjects with Successful Global Response, as determined by the Data Review Committee |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Global Response at Day 14 | Day 14 | The percentage of subjects with Successful Global Response, as determined by the Data Review Committee |
Countries
Belgium, Bulgaria, Canada, China, France, Germany, Greece, Israel, Italy, South Africa, South Korea, Spain, United States
Contacts
STUDY_DIRECTORDavid Angulo, MD
Scynexis, Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Absolute Neutrophil Count </= 500 per cubic millimeter | 2 Participants |
| Absolute Neutrophil Count > 500 per cubic millimeter | 34 Participants |
| Age, Continuous | 57.6 years STANDARD_DEVIATION 15.71 |
| Body Mass Index (BMI) | 26.54 kilograms per meter squared STANDARD_DEVIATION 12.28 |
| Echocardiography/MUGA at Baseline Abnormal - Clinically Significant | 1 Participants |
| Echocardiography/MUGA at Baseline Abnormal - Not Clinically Significant | 8 Participants |
| Echocardiography/MUGA at Baseline Normal | 19 Participants |
| Echocardiography/MUGA at Baseline Not Done | 30 Participants |
| Echocardiography/MUGA at Baseline Not Evaluable | 0 Participants |
| Electrocardiogram Interpretation at Baseline Abnormal - Clinically Significant | 2 Participants |
| Electrocardiogram Interpretation at Baseline Abnormal - Not Clinically Significant | 14 Participants |
| Electrocardiogram Interpretation at Baseline Normal | 12 Participants |
| Electrocardiogram Interpretation at Baseline Not Done | 10 Participants |
| Electrocardiogram Interpretation at Baseline Not Evaluable | 0 Participants |
| Electrocardiogram PR Interval at Baseline | 148.9 milliseconds STANDARD_DEVIATION 26.97 |
| Electrocardiogram QRS Interval at Baseline | 89.0 milliseconds STANDARD_DEVIATION 17.79 |
| Electrocardiogram QTcF Interval at Baseline | 416.2 milliseconds STANDARD_DEVIATION 23.07 |
| Electrocardiogram QT Interval at Baseline | 375.9 milliseconds STANDARD_DEVIATION 43.25 |
| Electrocardiogram RR Interval at Baseline | 692.8 milliseconds STANDARD_DEVIATION 164.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Height | 168.02 centimeters STANDARD_DEVIATION 10.744 |
| Left Ventricular Ejection Fraction at Baseline | 60.0 % of ejected blood from left ventricle STANDARD_DEVIATION 8.84 |
| Modified Acute Physiology and Chronic Health Evaluation (APACHE) II Score </= 20 | 62 Participants |
| Modified Acute Physiology and Chronic Health Evaluation (APACHE) II Score >20 | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 47 Participants |
| Retinal examination at Baseline Abnormal, due to Candida Infection | 0 Participants |
| Retinal examination at Baseline Abnormal, not due to Candida Infection | 8 Participants |
| Retinal examination at Baseline Normal | 40 Participants |
| Retinal examination at Baseline Not Done | 2 Participants |
| Risk factors for mortality Acute Kidney Injury | 8 Participants |
| Risk factors for mortality Broad Spectrum Antibiotics | 31 Participants |
| Risk factors for mortality Burns | 0 Participants |
| Risk factors for mortality Central Venous Catheter not removed | 12 Participants |
| Risk factors for mortality Diabetes mellitus | 19 Participants |
| Risk factors for mortality Dialysis | 10 Participants |
| Risk factors for mortality End stage renal disease | 6 Participants |
| Risk factors for mortality Gastrointestinal perforation | 4 Participants |
| Risk factors for mortality Hepatic Dysfunction | 5 Participants |
| Risk factors for mortality ICU admission | 9 Participants |
| Risk factors for mortality Immunosuppressive therapy | 9 Participants |
| Risk factors for mortality Major surgery | 10 Participants |
| Risk factors for mortality Mechanical Ventilation | 7 Participants |
| Risk factors for mortality Neutropenia (ANC </= 1500 cells per cu mm) | 3 Participants |
| Risk factors for mortality Other | 3 Participants |
| Risk factors for mortality Pancreatitis | 0 Participants |
| Risk factors for mortality Presence of septic shock | 4 Participants |
| Risk factors for mortality Source control within 24 Hours | 2 Participants |
| Risk factors for mortality Thrombocytopenia (platelets<150,000/uL) | 4 Participants |
| Risk factors for mortality Total Parenteral Nutrition | 6 Participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 14 Participants |
| Weight | 71.23 kilograms STANDARD_DEVIATION 22.331 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 36 | 3 / 32 |
| other Total, other adverse events | 27 / 36 | 28 / 32 |
| serious Total, serious adverse events | 20 / 36 | 20 / 32 |
Outcome results
None listed